Despite the success of modern signaling targeted drugs and immune checkpoint blockers, the cure of patients with advanced cancers is still hampered by the resistance of tumor cells against drugs and immune mechanisms. Increasing evidence indicates that this is not solely driven by genetic evolution, but also by the epigenetic adaptive plasticity of tumor cell phenotypes.

Current findings by us and others point to an understanding of cancer as a highly plastic system, in which tumor cell subpopulations dynamically switch between multiple identities depending on the current therapeutic and microenvironmental context. Interestingly, the underlying cell biologic principles seem to be similar across various cancer types. However, neither do we know the underlying molecular mechanisms, nor how we can influence them to overcome dynamic phenotype switching as a cause of therapy resistance.

At this central point the KFO337 comes into action. Our overall goal of is to comprehensively study the molecular mechanisms controlling phenotypic plasticity and immune escape in a distinct assembly of cancers and to reciprocally test the findings across the different cancer entities thereby opening new treatment avenues and strategies that modulate the phenotypic shift of tumor cells to prevent drug resistance when combined with established therapies.